The Caliciviridae is a family of positive-strand RNA viruses and consists of five genera designated: (1) Norovirus (with species Norwalk virus); (2) Sapovirus (with species Sapporo virus); (3) Vesivirus (with species, feline calicivirus and vesicular exanthema of swine virus); (4) Lagovirus (with species rabbit hemorrhagic disease virus and European brown hare syndrome virus) and (5) Nebovirus (with species Newbury-2 virus). The Caliciviruses Section in LID is focused on one major goal: lessen the disease burden from caliciviruses that cause disease in humans. Noroviruses are the primary focus of our research because they are the major calicivirus pathogens in humans. They cause the majority of epidemic gastroenteritis outbreaks and are second to rotaviruses as agents of severe diarrhea in infants and young children. They can cause chronic infection and life-threatening illness in immunocompromised individuals. Noroviruses are genetically-diverse and most human norovirus pathogens belong to either Genogroup I (GI) or Genogroup II (GII), with GII.4 as the predominant genotype. Because a major technical challenge in the study of these viruses is the inability to grow them in cultured cells, our laboratory has developed calicivirus replication systems and animal models to establish parameters of infection and immunity. This year we investigated the mini pig as an animal model in which to evaluate norovirus vaccines and therapeutic drugs. We continued our collaboration with a leading company in norovirus vaccine development, Takeda Vaccines Montana (formerly LigoCyte Pharmaceuticals, Inc.), to address the immunogenicity and broad reactivity of new norovirus vaccine candidates. One approach under consideration for the treatment of norovirus disease is therapeutic antibodies, and we have made progress in this area. In collaboration with Dr. Robert H. Purcell (LID), we generated the first norovirus-specific antibodies with putative neutralizing activity as demonstrated in the chimpanzee model before the model was discontinued. We are continuing to develop and map additional antibodies in the laboratory, generated by a variety of technologies including nanobody technology in collaboration with Dr. Viviana Parreo at INTA in Argentina. One goal is to map cross-reactive antigenic sites that might serve as targets for the design of broadly-protective vaccines. Two patents were filed this year for the unique antibodies generated in these projects, and studies are planned to evaluate their efficacy. This will be facilitated by the addition to our team this year of a gastroenterology medical fellow and an experienced postdoctoral fellow who will work together to evaluate identify therapeutic approaches that could be translated to clinical evaluation.